Modified chitosan oligosaccharide, composite decontamination preparation and preparation method thereof

Abstract

The invention relates to modified chitosan oligosaccharide, a composite decontamination preparation and a preparation method thereof, and belongs to the technical field of nuclide decontamination and daily chemicals. The raw materials mainly comprise AESA, OP-10, K12A, APG1214, LAO-30, modified chitosan oligosaccharide and the like. The modified chitosan oligosaccharide is carboxymethyl chitosan oligosaccharide, the water solubility is improved after modification, and tests show that the material has a good function of removing radionuclides from human skin. According to the compound decontamination preparation, actinide nuclide decontamination and cobalt and cesium decontamination efficiency verification proves that the decontamination efficiencies in 6-hour and 12-hour experimental groups respectively reach 85% and 65% or above. Skin stimulation experiments of the decontamination liquid prove that the decontamination liquid has no stimulation or damage to normal skin of a human body. A skin sensitization test proves that the guinea pig skin sensitization reaction grade is 0. The invention is mainly applied to emergency decontamination of radionuclide.

Description

Technical Field

[0001] The invention relates to a modified chitosan oligosaccharide, a composite disinfectant preparation and a preparation method thereof, and belongs to the technical field of nuclide disinfection and daily chemicals. Background Art

[0002] Radioactive nuclides are widely used in the fields of medicine, energy, military, scientific research, etc. Radioactive gases and aerosols are widely present in places where radioactive materials are produced, used and operated. The running, bubbling, dripping and leakage of radioactive liquids cause workers to contact and operate open nuclides. Although there are no clear incidents of nuclide spillage or contamination, it is inevitable that a small amount of radioactive nuclides will remain on the workers' bodies, thus causing them to be contaminated by radioactivity.

[0003] If the human body is exposed to small doses of radionuclides for a long time, it is possible to develop radiation diseases, mainly chronic radiation sickness, such as neurological symptoms (such as headache, dizziness, unsteady gait, etc.), digestive system symptoms (such as vomiting, loss of appetite, etc.), bone marrow hematopoiesis suppression, blood cell decline, bleeding and infection, etc. Therefore, when workers leave the radioactive workplace, they should clean their bodies to avoid long-term retention of radionuclides in the body, which will cause external radiation to the human body; at the same time, as time goes by, radionuclides may enter the body through the skin, and then cause internal radiation, which is more harmful.

[0004] Although there are some disinfection products at home and abroad, their disinfection efficiency is limited; the present invention intends to develop a compound preparation with modified chitosan oligosaccharide as the core to improve the ability and efficiency of disinfection on human skin. Summary of the invention

[0005] The present invention aims to provide a modified chitosan oligosaccharide, a composite cleaning preparation and a preparation method thereof, which can eliminate the contamination of radionuclides on the skin surface of the body and reduce the harm thereof.

[0006] A modified chitosan oligosaccharide for removing nuclides from the skin, wherein the modified chitosan oligosaccharide is a chitosan oligosaccharide with a molecular weight of less than 2000, specifically carboxymethyl chitosan oligosaccharide, and the molecular structure is as follows:

[0007] A composite disinfectant preparation prepared by using the modified chitosan oligosaccharide, wherein the raw materials for preparation contain the following components: pure water, fatty alcohol polyoxyethylene ether ammonium sulfate AESA, lauryl ammonium sulfate K 12A. Alkyl polyglycoside APG1214, cocoamidopropyl amine oxide LAO-30, polyoxyethylene sorbitan monolaurate Tween 20, alkyl dimethyl amine oxide OB-2, OA-12, sodium lauroyl sarcosinate LS-30, octylphenol polyoxyethylene ether OP-10, sodium chloride NaCl, disodium ethylenediaminetetraacetic acid EDTA-2Na, dipotassium ethylenediaminetetraacetic acid EDTA-2K, sodium ferric ethylenediaminetetraacetic acid EDTA-FeNa, pentasodium diethylenetriaminepentaacetic acid DTPA-5Na, tetrasodium hydroxyethylidene diphosphonic acid HEDP-4Na, and modified chitosan oligosaccharide.

[0008] In the composite disinfectant prepared by modified chitosan oligosaccharide of the present invention, the proportion of each component in 1000 parts by weight of the raw materials is: 650-800 parts of pure water, 100-150 parts of AESA, 10-20 parts of OP-10, 5-15 parts of K 12 A, 5~15 parts of APG1214, 3~10 parts of LAO-30, 3~10 parts of Tween 20, 3~10 parts of LS-30, 25~40 parts of NaCl, 15~40 parts of glycerol, 3~10 parts of DTPA-5Na, 5~10 parts of EDTA-2Na, 1~3 parts of EDTA-2K, 2~10 parts of HEDP-4Na, 1~3 parts of EDTA-FeNa, 1~5 parts of modified chitosan oligosaccharide, 0~3 parts of sodium citrate, 0~5 parts of flavor, 0~2 parts of 2.5% kason preservative, 0~1 part of amino acid moisturizer, 0~1 part of vitamin B6, 0~1 part of pigment.

[0009] In the composite disinfectant prepared by modified chitosan oligosaccharide of the present invention, the ratio of each component to 1000 parts by weight of the raw materials is: 725 parts of pure water, 135 parts of AESA, 15 parts of OP-10, 13 parts of K 12 A, 10 parts of APG1214, 8 parts of LAO-30, 7 parts of Tween 20, 5 parts of LS-30, 30 parts of NaCl, 20 parts of glycerin, 9 parts of DTPA-5Na, 8 parts of EDTA-2Na, 2 parts of EDTA-2K, 5 parts of HEDP-4Na, 1 part of EDTA-FeNa, 3 parts of modified chitosan oligosaccharides, 1 part of sodium citrate, 1.3 parts of flavor, 1 part of 2.5% kason preservative, 0.5 parts of amino acid moisturizer, 0.2 parts of vitamin B6, 0.01 parts (1 drop) of pigment.

[0010] The preparation method of the composite disinfectant preparation is: Liquid A: Add 4 / 7 of the total weight of pure water into a container, heat to 65°C, stop heating, add EDTA-2Na, stir to fully dissolve; add AESA, stir to fully dissolve; add K 12A, stir to fully dissolve; add APG1214, stir to fully dissolve; add LAO-30, stir to fully dissolve; add 7 parts of Tween 20, stir to fully dissolve; add LS-30, stir to fully dissolve; add glycerol, stir to fully dissolve; Liquid B: Add 2 / 7 of the total weight of pure water into a container, heat to 50°C, stop heating, add NaCl, stir to fully dissolve; add HEDP-4Na, stir to fully dissolve; add EDTA-2K, stir to fully dissolve; add EDTA-FeNa, stir to fully dissolve; add DTPA-5Na, stir to fully dissolve; Liquid C: Add the remaining water into the container, heat to 35°C, stop heating, add modified chitosan oligosaccharide, stir to fully dissolve; add flavor, stir to fully dissolve; add 2.5% kasone preservative, stir to fully dissolve; add amino acid moisturizer, vitamin B6, pigment, stir to fully dissolve; After the above three solutions are prepared and cooled to a temperature of 15-30℃, first slowly add liquid B into liquid A, stirring while adding, and mix thoroughly; then add liquid C, stirring while adding, and mix thoroughly. Let it stand for more than 24 hours to ensure that all bubbles are expelled, and finally form a viscous, colored solution with a pleasant smell.

[0011] The present invention adopts a new material modified chitosan oligosaccharide as the core material for decontamination of radionuclides from human skin. The material is prepared by degrading chitosan to make its molecular weight less than 2000, and then modifying chitosan oligosaccharide to obtain carboxymethyl chitosan oligosaccharide (-COOH), namely modified chitosan oligosaccharide. Experiments have found that modified chitosan oligosaccharide has a good function of removing radionuclides from human skin, and has a good decontamination effect on transition metals and actinide nuclides. The decontamination efficiency of actinide nuclides, cobalt and cesium has been verified, and the decontamination efficiency in the 6h and 12h experimental groups reached 80% and 60% respectively. The concentration of modified chitosan oligosaccharide has little effect on its decontamination efficiency.

[0012] A compound preparation is prepared by modifying chitosan oligosaccharide with new materials and then supplemented with some chelating agents, complexing agents, surfactants, auxiliary agents and other materials. The functions of each component are mutually complementary and enhanced, so that the compound preparation has a strong ability to remove radioactive nuclides from human skin, which is more efficient and practical than the previous formula. This formula can be used for the prevention and treatment of daily radioactive nuclide contamination of human skin, and can also be used for emergency treatment of nuclear accident contamination. It has the dual functions of nuclide decontamination and skin decontamination.

[0013] Although there are some disinfection products at home and abroad, the disinfection efficiency is limited. The compound preparation product with modified chitosan oligosaccharide as the core developed by the present invention has been mass-produced, which can improve the ability and efficiency of skin nuclide disinfection. The verification of actinide nuclide disinfection, cobalt and cesium disinfection efficiency has proved that the disinfection efficiency in the 6h and 12h experimental groups reached more than 85% and 65% respectively. The results of the skin irritation experiment of the composite disinfection preparation proved that it had no irritation or damage to the normal human skin. The skin sensitization test of the composite disinfection preparation proved that the sensitization reaction level to the guinea pig skin was 0. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Molecular structure of modified chitosan oligosaccharide carboxymethyl chitosan oligosaccharide. DETAILED DESCRIPTION

[0015] The invention discloses a broad-spectrum radionuclide body skin contamination cleaning agent formula with modified chitosan oligosaccharide as a core component and a preparation method thereof, which can eliminate the contamination of radionuclide on the body skin surface and reduce the harm thereof.

[0016] 1. Preparation and decontamination efficiency of modified chitosan oligosaccharides Modified chitosan oligosaccharide refers to a material obtained by degrading chitosan to obtain chitosan oligosaccharide with a molecular weight less than 2000, and then subjecting it to carboxymethylation (-COOH), namely, carboxymethyl chitosan oligosaccharide.

[0017] 1. Preparation of modified chitosan oligosaccharides - degradation and modification of chitosan ①Degrade chitosan to a molecular weight of <2000 The molecular weight of chitosan is usually around hundreds of thousands. Due to the effect of hydrogen bonds in its molecules, it can only be dissolved in a few dilute acid solutions, but not directly dissolved in water. It can be degraded into chitosan oligosaccharides with a molecular weight of <2000 by irradiation decomposition (a method for degrading high molecular weight chitosan by interaction of electron beam irradiation and radiation sensitizer; application (patent) number: CN201610127153.1; application date: 2016-03-07; authorization announcement number: CN105732843B) or enzymatic hydrolysis (a method and application of preparing chitosan oligosaccharides in one step by enzymatic hydrolysis using shrimp and crab shells as raw materials; application (patent) number: CN201510232838.8; application date: 2015-05-08; authorization announcement number: CN104829749B). This technology is relatively mature, and chitosan oligosaccharides with a molecular weight of <2000 after degradation can also be directly purchased, such as the related products produced by Shandong Weikang Biomedical Technology Co., Ltd.

[0018] ② Modify chitosan oligosaccharide and carboxymethylate it (-COOH) Prepare an isopropanol solution containing sodium hydroxide in a container, so that the concentration of sodium hydroxide is 40%; add the chitosan oligosaccharide with a molecular weight of <2000 after degradation; slowly drop the isopropyl acetic acid solution into the container under stirring, and continue stirring and reacting for 3 hours after the addition. After the reaction is completed, add concentrated hydrochloric acid to the reaction material, adjust the pH value of the material to 6-7, filter, and wash the filter cake with anhydrous ethanol for 3 times. After drying the washed filter cake below 50°C, obtain the primary product of carboxymethyl chitosan oligosaccharide, and then purify it to obtain the modified chitosan oligosaccharide carboxymethyl chitosan oligosaccharide, the molecular structure of which is as follows: Figure 1 .

[0019] ③Characteristics of modified chitosan oligosaccharide Modified chitosan oligosaccharide (carboxymethyl chitosan oligosaccharide) is a water-soluble chitosan oligosaccharide derivative and an amphoteric polyelectrolyte. After modification, its water solubility is improved, especially its solubility in neutral and alkaline solutions is significantly enhanced, making it have film-forming, thickening, moisturizing, chelating, antibacterial, and anti-infection properties.

[0020] 2. Experimental study on the removal of nuclides by modified chitosan oligosaccharides ①Preparation of modified chitosan oligosaccharide solvent The modified chitosan oligosaccharide obtained above was dissolved in water to prepare 1%, 3% and 5% by mass of water solvent respectively for later use.

[0021] ② Use the prepared solvent to perform radionuclide decontamination The experimental materials and methods are the same as those in “Instructions for the present invention (II) Preparation of composite disinfectant preparations using modified chitosan oligosaccharides and verification experiment 4. Verification of the efficiency of skin radionuclide disinfectant”.

[0022] ③ Experimental results Table 1 Results of the skin radionuclide decontamination experiment using 1% modified chitosan oligosaccharide

[0023] Table 2 Results of the skin nuclide decontamination experiment using 3% modified chitosan oligosaccharide

[0024] Table 3 Results of the skin nuclide decontamination experiment using 5% modified chitosan oligosaccharide

[0025] From the modified chitosan oligosaccharide solvent decontamination efficiency verification results table 1-3, it can be seen that the material has a good function of removing radionuclides from human skin, and has a good decontamination effect on transition metals and actinide nuclides. The decontamination efficiency of actinide nuclides, cobalt and cesium decontamination proves that the skin nuclide decontamination efficiency in the 6h and 12h experimental groups reached more than 80% and 60% respectively. The concentration of modified chitosan oligosaccharide has little effect on the skin nuclide decontamination efficiency.

[0026] (II) Preparation of composite disinfectant preparations with modified chitosan oligosaccharides and verification experiments 1. Decontamination solution formula components (Table 4): The main ingredients of the decontamination liquid include: pure water, fatty alcohol polyoxyethylene ether ammonium sulfate (AESA), lauryl ammonium sulfate (K 12 A), alkyl polyglycoside (alkyl glycoside) (APG1214), coconut oil amide propyl amine oxide (LAO-30), polyoxyethylene sorbitan monolaurate (Tween 20), alkyl dimethyl amine oxide (OB-2, OA-12), sodium lauroyl sarcosinate (LS-30), octylphenol polyoxyethylene ether (OP-10, TX-10), sodium chloride (NaCl), disodium ethylenediaminetetraacetic acid (EDTA-2Na), dipotassium ethylenediaminetetraacetic acid (EDTA-2K), sodium ferric ethylenediaminetetraacetic acid (EDTA-FeNa), pentasodium diethylenetriamine pentaacetic acid (DTPA-5Na), tetrasodium hydroxyethylidene diphosphonic acid (HEDP-4Na), modified chitosan oligosaccharide, sodium citrate, glycerol (glycerin), isothiazolinone (kason), amino acid moisturizer, pigment, flavor.

[0027] The proportion of each component is adjustable, and the rest is made up with pure water.

[0028] Table 4 Components and contents of three skin radionuclide composite decontamination preparations

[0029] 2. Formula ingredients and raw materials (Table 5): Functions of other main components: Tetrasodium hydroxyethylidene diphosphonate, abbreviated as HEDP-4Na, chemical formula: C2H4Na4O7P2, molar mass 294, white solid powder, easily soluble in water, belongs to the organic phosphonate class of scale inhibitors and corrosion inhibitors, can form stable complexes with a variety of metal ions, and can dissolve oxides. Pentasodium diethylenetriamine pentaacetate, abbreviated as DTPA-5Na, chemical formula: C 14 H 23 N3Na5O 10 , molar mass 508.3, easily soluble in water, an organic compound that can quickly form water-soluble complexes or stable chelates with radioactive metal ions, and has a wide range of complexing properties. Disodium ethylenediaminetetraacetate, abbreviation: EDTA-2NA, chemical formula: C 10 H 14N2Na2O8▪2H2O, molar mass 372.24, easily soluble in water, solubility 0.3mol / L, 11.1g can be dissolved in every 100ml water. It is an organic compound with multidentate ligands, containing carboxyl and amino groups, with extensive complexing properties, and can form stable chelates with radioactive metal ions. Fatty alcohol polyoxyethylene ether ammonium sulfate, abbreviated as AESA, is easily soluble in water, an anionic surfactant, and has excellent cleaning, emulsification and foaming properties. Dodecyl ammonium sulfate, abbreviated as K 12A, easily soluble in water, anionic surfactant, with excellent cleaning and foaming properties. Alkyl polyglycoside (APG1214) is a multi-carbon APG with 12 to 14 carbons in the alkyl glycoside series. It has high foaming properties and is a non-ionic surfactant made from renewable plant raw materials. It has mild properties, little irritation to the human body, softens the skin, has no irritation to the eyes, and has good ecological compatibility. During low-temperature storage, a small amount of solids will precipitate or the appearance will be turbid due to the influence of monoglycoside and high pH value, but it has no negative impact. The turbidity disappears when the temperature is increased or the pH is adjusted to 7-9. Coconut oil amide propyl amine oxide (LAO-30) is a colorless or slightly yellow low-viscosity liquid with a pH value (1% aqueous solution): 5-7.5, and rich and stable foam. Polyoxyethylene sorbitan monolaurate (Tween 20) is a yellow or amber clear oily liquid with a special odor and a weak bitter taste. Its relative density is 1.01, boiling point>100℃, flash point is 321℃, and refractive index is 1.472. It contains a large number of hydrophilic groups in the molecule and is miscible with water, ethanol, methanol and ethyl acetate. It is a non-ionic surfactant with emulsification, diffusion, solubilization and stabilization functions. OP-10 is an octylphenol polyoxyethylene ether containing 10 ethoxy groups, also known as alkylphenol polyoxyethylene (10) ether, referred to as TX-10, OP-10, with a molecular weight of 646. It is a colorless or light yellow oily liquid that dissolves in water and is transparent. It has good emulsification, drying, dispersion, decontamination and antistatic capabilities, and good hard water resistance. It is acid and alkali resistant. It can be mixed with various surfactants. Sodium lauroyl sarcosinate (LS-30) is a colorless to light yellow transparent liquid, mild, safe and low irritation. It has excellent stability and foaming properties in the pH range from strong alkaline to weak acid. It has low degreasing power, moisturizing and non-tight skin feel, good compatibility, and can be combined with other anionic surfactants to reduce irritation and improve foaming properties. OB-2 (alkyl dimethyl amine oxide) is a surfactant synthesized using dodecyl dimethyl tertiary amine as the main raw material. Appearance: colorless or slightly yellow low viscosity liquid, pH value (1% aqueous solution): 5-8, odorless, colorless or slightly yellow low viscosity liquid, soluble in water, rich and stable foam, antistatic, soft and refreshing. Glycerol, also known as glycerin, chemical formula: C3H8O3, molar mass 92, miscible with water and ethanol, neutral in aqueous solution, is a colorless, odorless, sweet, clear and thick liquid. Isothiazolinone, also known as kason, chemical formula: C8H9ClN2O2S2, molar mass: 264.75, has a strong inhibitory and killing effect on common bacteria, fungi, algae, etc. by breaking protein bonds.

[0030] The skin cleaning preparation uses modified chitosan oligosaccharide as the core ingredient and is used in combination with a variety of complexing agents to increase the complexing ability of the entire series of nuclides, thereby increasing the decontamination ability and decontamination breadth. The active agents mainly include AESA, K 12A, LS-30, APG1214, LAO-30, Tween 20, OP-10, OB-2, a total of 8 types, anionic surfactants and non-ionic surfactants, with synergistic effects, can reduce surface tension efficiency, increase the solubility of radioactive substances and common body stains in aqueous solutions, achieve the purpose of activating nuclides and dirt, and make them easier to remove. At the same time, auxiliary ingredients such as glycerol, amino acid moisturizer, vitamin B6, etc. are added to lubricate the body skin; auxiliary ingredients such as pigments, kasone preservatives, and flavors are added to achieve functions such as changing the color of the preparation, preservation, and fragrance enhancement, so that users have a better visual and taste experience.

[0031] Table 5 Skin radionuclide decontamination preparations, reagents, manufacturer specifications

[0032] 3. Preparation method of disinfectant The weight ratio of 1000 components is: 725 parts pure water, 135 parts AESA, 15 parts OP-10, 13 parts K 12 A, 10 parts of APG1214, 8 parts of LAO-30, 7 parts of Tween 20, 5 parts of LS-30, 30 parts of NaCl, 20 parts of glycerol, 9 parts of DTPA-5Na, 8 parts of EDTA-2Na, 2 parts of EDTA-2K, 5 parts of HEDP-4Na, 1 part of EDTA-FeNa, 3 parts of modified chitosan oligosaccharide, 1 part of sodium citrate, 1.3 parts of flavor, 1 part of 2.5% kason preservative, 0.5 parts of amino acid moisturizer, 0.2 parts of vitamin B6, 0.01 parts (1 drop) of pigment. "For example.

[0033] Liquid A: Add 425 parts of pure water into a container, heat to 65°C, stop heating, add 8 parts of EDTA-2Na, stir to fully dissolve; add 135 parts of AESA, stir to fully dissolve; add 15 parts of K 12 A, stir to fully dissolve; add 10 parts of APG1214, stir to fully dissolve; add 8 parts of LAO-30, stir to fully dissolve; add 7 parts of Tween 20, stir to fully dissolve; add 5 parts of LS-30, stir to fully dissolve; add 20 parts of glycerol, stir to fully dissolve; Solution B: Add 200 parts of water to a container, heat to 50°C, stop heating, add 30 parts of NaCl, stir to fully dissolve; add 5 parts of HEDP-4Na, stir to fully dissolve; add 2 parts of EDTA-2K, stir to fully dissolve; add 1 part of EDTA-FeNa, stir to fully dissolve; add 9 parts of DTPA-5Na, stir to fully dissolve; Liquid C: Add 100 parts of water into a container, heat to 35°C, stop heating, add 3 parts of modified chitosan oligosaccharide, stir to fully dissolve; add 1.3 parts of flavor, stir to fully dissolve; add 1 part of 2.5% Kasong preservative, stir to fully dissolve; add 0.5 parts of amino acid moisturizer, 0.2 parts of vitamin B6, 0.01 parts (1 drop) of pigment, stir to fully dissolve.

[0034] After the above three solutions are prepared and cooled to a temperature (15~30℃), first slowly add liquid B into liquid A, stirring while adding, and mix thoroughly; then add liquid C, stirring while adding, and mix thoroughly. Let it stand for more than 24 hours to ensure that all bubbles are discharged, and finally form a viscous, colored solution with a pleasant smell.

[0035] Note: The stirring speed and stirring time vary according to the equipment, and the full dissolution of the solvent is used as an indicator; full dissolution means that the solvent is completely dissolved in the aqueous solution, without precipitation, flocculation, agglomeration, and clarity; the order of solvent addition should be strictly followed, otherwise there may be an intermediate reaction, affecting the final product decontamination efficiency and finished product effect; AESA dissolves slowly, so be sure to stir it fully to ensure complete dissolution. If necessary, a homogenizer (emulsifier) ​​can be used for dissolution; multiple reagents should not be added at the same time and then stirred to avoid reactions. After liquid A, liquid B, and liquid C are heated to the specified temperature, the heating should be stopped. The solution temperature can be used to accelerate dissolution and disinfection at the same time; after all the solvents that need to be added are dissolved, the solution temperature is basically close to room temperature or slightly higher than room temperature, and then the solutions can be added.

[0036] 4. Verification of the efficiency of skin radionuclide decontamination solution 1) Actinide nuclide decontamination method: The contaminated nuclides in this experiment are mixed solutions of uranium and thorium, and the medium is 0.5Mol / L HNO3 solution. A certain weight of the contaminated solution is applied to the surface of the pig skin, and then decontaminated with actinide nuclide surface contamination decontamination solution after 0h, 6h, and 12h.

[0037] Detection method: Use ICP-MS instrument to detect the content of uranium and thorium in the contaminated liquid and the decontaminated liquid respectively, measure and read, and revise the errors in the experiment.

[0038] ①Material preparation: pig skin, uranium standard solution, thorium standard solution, shaker, disinfection box, 50ml solution tube, disinfection reagent, ICP-MS, label paper, pen, tweezers, waste bucket, cotton swab, pipette, pipette tip, high-precision electronic balance, 0.5M HNO3 solution, etc.; ② Cut the pig skin (not scalded with boiling water) into appropriate size and put it into the disinfection box, label it and number it; set up 3 parallel control samples for each group, set up three experimental groups at 0h, 6h and 12h, and set up a control group for each experimental group without pig skin; ③ Prepare actinide nuclide poisoning solution: Mix 0.1ml / 1g of uranium and thorium, add 0.5M HNO3 to dilute to 10PPM, and use it as the poisoning stock solution. (The specific preparation method is not repeated, but the concentration should be accurate) ④ Take 1ml / 1g actinide nuclide solution (uranium and thorium), inject it onto the pig skin surface with a pipette and spread it evenly; for each control group, wait until the disinfection treatment is carried out, and then directly inject it onto the disinfection reagent in the disinfection box; ⑤ The 0h group started treatment 5-10 minutes after exposure, the 6h group started treatment 6 hours after exposure, and the 12h group started treatment 12 hours after exposure; ⑥ Apply 20 ml of radionuclide decontamination hand washing preparation to the surface of pig skin (the control group directly applies it to the disinfection box); put the disinfection box on the shaker, set it to 200 rpm, and disinfect for 10 minutes; collect the disinfection liquid after disinfection.

[0039] ⑦ Repeat step ⑥ 2 times according to the disinfection situation; collect a total of 60ml / 60g of disinfection solution and mix well; ⑧Take 1ml / 1g of solution ⑦, dilute it to 40ml / 40g with 0.5M HNO3 solution, and shake it evenly on a shaker; ⑨ Take 1ml / 1g of solution ⑧, dilute it to 40ml / 40g with 0.5M HNO3 solution, and shake it evenly on a shaker; ⑩ Place solution 9 on the ICP-MS for measurement, read the total number of uranium and thorium nuclides respectively, and record them; the reading of the control group is the nuclide contamination amount, and the reading of the experimental group is the decontamination amount. The decontamination efficiency = decontamination liquid / contamination liquid × 100%; enter the data into the database and use the formula to calculate the decontamination efficiency.

[0040] 2) Cobalt and cesium decontamination experimental method: The contaminated radionuclides in this experiment are cobalt and cesium mixed solutions, and the medium is aqueous solution. Take 0.5ml of the contaminated solution and apply it to the surface of the pig skin. Use the radionuclide decontamination hand washing preparation to decontaminate after 0h, 6h, and 12h respectively.

[0041] Detection method: Use a gamma spectrometer to detect the radioactive content of cobalt and cesium in the pig skin after poisoning and disinfection, measure and read, and revise the errors in the experiment.

[0042] ①Material preparation: pig skin, transition metal nuclide solution, shaker, disinfection box, disinfection reagent, high-purity germanium gamma spectrometer, label paper, pen, non-woven fabric, tweezers, waste bucket, cotton swab, pipette, pipette tip, etc.; ② Cut the pig skin (without scalding) into appropriate size and put it into the disinfection box, label it and number it; set 3 parallel control samples for each group, set 0h, 6h and 12h three groups; then put it on the high-purity germanium gamma spectrometer for measurement, the measurement time is 200s, read the background total count and count rate of cesium, cobalt and manganese respectively, and record them (multiple experiments show that the background total count and count rate are 0); ③ Take 1 ml (the amount can be changed according to the activity) of transition metal nuclide solution, inject it into the surface of pig skin with a pipette and spread it evenly; ④ Place the pigskin disinfection box with the nuclide applied on the high-purity germanium gamma spectrometer for measurement. The measurement time is 200s. Read the total count and count rate of cesium, cobalt, and manganese contamination nuclides and record them; ⑤ The 0h group started treatment 5-10 minutes after exposure, the 6h group started treatment 6 hours after exposure, and the 12h group started treatment 12 hours after exposure; ⑥ Apply an appropriate amount of radionuclide decontamination hand washing preparation to the surface of the pig skin and spread it with a cotton swab; place the disinfection box on a shaker, set it to 200 rpm, and disinfect for 10 minutes; pour out the disinfection solution after disinfection.

[0043] ⑦ Repeat step ⑥ once according to the disinfection results; if the disinfection effect is not good, repeat step ⑥ once more; disinfection can be repeated up to 3 times; ⑧ Wipe the disinfected pigskin with non-woven fabric and put it into a clean disinfection box, then place it on a high-purity germanium gamma spectrometer for measurement. The measurement time is 200 seconds. Read the total counts and count rates of cesium, cobalt, and manganese after disinfection and record them; ⑨Enter the data into the database and use the formula to calculate the decontamination efficiency. Decontamination efficiency = (1-after decontamination / after contamination) × 100%.

[0044] 3) Iodine decontamination experimental method: The contaminating radionuclide in this experiment is iodine solution, and the medium is aqueous solution. Take 1ml of the contaminating solution and apply it to the surface of the pig skin. Use the radionuclide decontamination hand washing preparation for decontamination after 0h, 6h, and 12h respectively.

[0045] Detection method: Use a low-energy gamma spectrometer to detect the radioactive content of iodine in the pig skin after poisoning and disinfection, measure and read, and revise the errors in the experiment.

[0046] ①Material preparation: pig skin, iodine radionuclide solution, shaker, disinfection box, disinfection reagent, high-purity germanium gamma spectrometer, label paper, pen, non-woven fabric, tweezers, waste bucket, cotton swab, pipette, pipette tip, etc.; ② Cut the pig skin (not scalded in boiling water) into appropriate size and put it in the disinfection box, label it and number it; set up 3 parallel control samples for each group, set up three groups of 0h, 6h and 12h; then put it on the low-energy high-purity germanium gamma spectrometer for measurement, the measurement time is 200s, read the total background count and count rate of iodine, and record them (multiple experiments show that the total background count and count rate are both 0); ③ Take 1 ml (the amount can be changed according to the activity) of iodine radionuclide solution, inject it into the surface of pig skin with a pipette and spread it evenly; ④ Place the pigskin disinfection box with the nuclide applied on the high-purity germanium gamma spectrometer for measurement. The measurement time is 200s. Read the total count and count rate of the iodine-contaminated nuclides and record them. ⑤ The 0h group started decontamination 5-10 minutes after exposure, the 6h group started decontamination 6 hours after exposure, and the 12h group started decontamination 12 hours after exposure; ⑥ Apply an appropriate amount of radionuclide decontamination hand washing preparation to the surface of the pig skin and spread it with a cotton swab; place the disinfection box on a shaker, set it to 200 rpm, and disinfect for 10 minutes; pour out the disinfection solution after disinfection.

[0047] ⑦ Repeat step ⑥ once according to the disinfection results; if the disinfection effect is not good, repeat step ⑥ once more; disinfection can be repeated up to 3 times; ⑧ Wipe the disinfected pigskin with non-woven fabric and put it into a clean disinfection box, then place it on a high-purity germanium gamma spectrometer for measurement. The measurement time is 200 seconds. Read the total count and count rate of iodine after disinfection and record them; ⑨Enter the data into the database and use the formula to calculate the decontamination efficiency. Decontamination efficiency = (1-after decontamination / after contamination) × 100%.

[0048] Table 6 Radionuclide decontamination efficiency of three skin radionuclide composite decontamination preparations

[0049] From the radionuclide decontamination efficiency of the three formulas of skin radionuclide composite decontamination preparations in Table 6, it can be seen that the skin radionuclide composite decontamination preparations prepared with modified chitosan oligosaccharides have good functions of removing radionuclides from human skin. The verification of actinide radionuclide decontamination, cobalt and cesium decontamination efficiency has proved that the decontamination efficiency in the 6h and 12h experimental groups reached more than 85% and 65% respectively.

[0050] 5. Results of the skin irritation test of disinfectant The prepared radionuclide decontamination hand-washing preparation was subjected to an animal irritation experiment. Three adult male white rabbits (experimental white rabbits purchased in the market) were selected, and the same rabbit was used for left and right control. The control side was smeared with normal saline, and the experimental side was smeared with the prepared radionuclide decontamination hand-washing preparation. The preparation was applied to the rabbit's ears, eyes, exposed skin, skin wounds and other parts respectively; the changes in the white rabbit's smeared parts before application, 0h, 1h, 4h, 12h, 24h, 48h, 72h and 120h after application were qualitatively judged and quantitatively scored. The scoring items include whether the skin and ears are red, swollen, inflamed, etc.; whether the eyes are red, swollen, congested, etc.; whether the wounds are red, swollen, inflamed, and healing is delayed. The experimental results show that the prepared radionuclide decontamination hand-washing preparation did not cause irritation reactions in the ears, eyes, exposed skin, and skin wounds of the white rabbits.

[0051] Taking the rabbit naked skin stimulation experiment as an example, the specific rules for qualitative judgment and quantitative scoring are explained (Table 7): Method for applying radionuclide decontamination hand washing preparation on the experimental side skin: One day before the test, shave 10cm×15cm area of ​​rabbit hair on the two parts to be applied, used as test and observation parts, add 0.5ml of radionuclide decontamination hand washing preparation to the two parts to be applied, cover each part to be applied with 2.5cm×2.5cm gauze, and then fix it with adhesive tape to form a patch. Remove the patch after 4 hours, wash with warm water and wipe dry.

[0052] Method for applying normal saline to the skin on the control side: Apply 0.5 ml of normal saline to the area to be applied on the control side. The operation method is the same as the method for applying the radionuclide decontamination hand washing preparation on the experimental side.

[0053] Observe the skin reaction under full-spectrum light at 0h, 1h, 4h, 12h, 24h, 48h, 72h and 120h after removing the patch, and describe and score the skin erythema and edema reactions at each contact site at each specified time according to the scoring system given in Table 7.

[0054] Table 7 Skin reaction scoring system

[0055] After scoring at 72h, add up all the erythema and edema scores caused by the test sample of each animal at 24h, 48h and 72h, and then divide the sum of all scores by 6 (two test side / control side application sites, 3 time points) to calculate the primary irritation score of the test material of a certain animal. Add up all the primary irritation scores of each animal and divide them by the total number of animals (3 rabbits) to obtain the primary irritation index of the test sample. According to the irritation reaction type corresponding to the irritation index given in Table 8, report the corresponding reaction type (Table 8).

[0056] Table 8 Types of stimulation responses corresponding to primary or cumulative stimulation index in rabbits

[0057] The test results show that during the 72-day observation period, the prepared radionuclide decontamination hand washing preparation did not show any irritation reactions such as erythema and edema at the application site on the reaction test side / control side, and the irritation reaction to the rabbit skin was 0 points. The primary irritation index of the test sample was 0, and the reaction type was extremely mild irritation. That is, the irritation reaction type of the prepared radionuclide decontamination hand washing preparation to the rabbit skin was extremely mild irritation.

[0058] At the same time, the prepared radionuclide decontamination hand washing preparation was also subjected to a human skin irritation experiment. Several people were selected to apply the radionuclide skin decontamination preparation on the body surface, wash, rinse with water after 1 minute, and observe the changes in the body skin. The experimental results showed that no abnormality occurred on the body skin of all the experimenters, proving that it has no irritation or damage to normal human skin.

[0059] 6. Skin sensitization test The prepared compound preparation was subjected to an animal skin sensitization test, and guinea pigs were selected as the test animals. Both international and national standards recommend the use of albino guinea pigs to contact the test material or its extract to induce and stimulate the evaluation of skin sensitization reactions.

[0060] Experimental group setting: 15 guinea pigs were selected, of which 10 were for the experimental sample group and 5 were for the negative control group.

[0061] Preparation of test samples: Take 5 ml of the prepared radionuclide skin decontamination preparation, which is the test sample.

[0062] Induction: drip the test sample onto a 2.5×2.5cm sheet of filter paper, fix it on the induction site of the corresponding group of guinea pigs (experimental guinea pigs purchased from the market), cover it with gauze and fix it with adhesive tape, remove the bandage and apply the patch after 6 hours, wash it with warm water and wipe it dry. Repeat this step for 3 consecutive days in a week, and operate in the same way for 3 weeks. The control group animals were operated in the same way with 0.9% sodium chloride injection.

[0063] Provocation: Depilate the guinea pig's back 13 days after the last induction patch. 24 hours later, drip 0.9% sodium chloride injection or 0.5 ml of the test sample onto a 2.5×2.5 cm sheet of filter paper, fix it to the provocation site of the guinea pig in the corresponding group, cover it with gauze and fix it with adhesive tape. Remove the bandage and apply the patch 6 hours later, wash it with warm water and wipe it dry.

[0064] Observation indicators: 24h and 48h after stimulation, the stimulation site was scored according to the Magnusson and Kligman grading standard given in Table 9.

[0065] Table 9 Magnusson and Kligman grading standard table

[0066] Sensitization is indicated when the grade in the control group animals is less than 1 and the grade in the test group animals is greater than or equal to 1. If the grade in the control group animals is greater than or equal to 1, sensitization is considered when the reaction of the test group animals exceeds the most severe reaction in the control animals.

[0067] The test results showed that the prepared compound preparation and 0.9% sodium chloride injection had a 0-level sensitization reaction to the guinea pig skin; the sensitization rate of the guinea pig skin in the test sample group and the negative control group was 0, and there was no obvious change in the skin.

[0068] 7. Test results of other indicators of disinfectant The decontamination liquid has no stratification, no obvious suspended matter or precipitation, no mechanical impurities, transparent liquid, and no odor. The stability test results show that after being stored at 40°C for 24 hours and returning to room temperature, there is no stratification, no precipitation, no odor or discoloration, and no turbidity; after being stored at -5°C for 24 hours and returning to room temperature, there is no stratification, no precipitation, no discoloration, and no turbidity. The total effective content of active ingredients is greater than 7%, the pH is neutral, the formaldehyde content is far less than 500mg / kg, and toxic and harmful substances such as methanol, mercury, lead, arsenic, cadmium and dioxane are not detected. The total colony count is less than 10CFU / g, and the mold and yeast are less than 10CFU / g. Heat-resistant Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa are not detected.

Claims

1. A modified chitosan oligosaccharide for removing skin nuclides, characterized in that: The modified chitosan oligosaccharide is a material obtained by carboxylating -COOH of chitosan oligosaccharide with a molecular weight of less than 2000, namely, carboxymethyl chitosan oligosaccharide, and the molecular structure is as follows: 。 2. A composite disinfectant preparation prepared using the modified chitosan oligosaccharide according to claim 1, characterized in that: The preparation raw materials contain the following components: pure water, fatty alcohol polyoxyethylene ether ammonium sulfate AESA, ammonium lauryl sulfate K12A, alkyl polysaccharide APG1214, coconut oil amide propyl amine oxide LAO-30, polyoxyethylene sorbitan monolaurate, i.e. Tween 20, alkyl dimethyl amine oxide OB-2, OA-12, sodium lauroyl sarcosinate LS-30, octylphenol polyoxyethylene ether, i.e. OP-10, sodium chloride NaCl, disodium ethylenediaminetetraacetic acid EDTA-2Na, dipotassium ethylenediaminetetraacetic acid EDTA-2K, sodium iron ethylenediaminetetraacetic acid EDTA-FeNa, pentasodium diethylenetriaminepentaacetic acid DTPA-5Na, tetrasodium hydroxyethylidene diphosphonic acid HEDP-4Na and modified chitosan oligosaccharide.

3. The composite disinfectant preparation according to claim 2, characterized in that: The proportions of each component in 1000 parts by weight of the raw materials are: 650-800 parts of pure water, 100-150 parts of AESA, 10-20 parts of OP-10, 5-15 parts of K12A, 5-15 parts of APG1214, 3-10 parts of LAO-30, 3-10 parts of Tween 20, 3-10 parts of LS-30, 25-40 parts of NaCl, 15-40 parts of glycerol, 3-10 parts of DTPA-5Na, 5-10 parts of EDTA-2Na, 1-3 parts of EDTA-2K, 2-10 parts of HEDP-4Na, 1-3 parts of EDTA-FeNa, 1-5 parts of modified chitosan oligosaccharide, 0-3 parts of sodium citrate, 0-5 parts of flavor, 0-2 parts of 2.5% kason preservative, 0-1 parts of amino acid moisturizer, 0-1 parts of vitamin B6, and 0-1 parts of pigment.

4. The composite disinfectant preparation according to claim 3, characterized in that: The proportion of raw material components in 1000 parts by weight is: 725 parts of pure water, 135 parts of AESA, 15 parts of OP-10, 13 parts of K12A, 10 parts of APG1214, 8 parts of LAO-30, 7 parts of Tween 20, 5 parts of LS-30, 30 parts of NaCl, 20 parts of glycerol, 9 parts of DTPA-5Na, 8 parts of EDTA-2Na, 2 parts of EDTA-2K, 5 parts of HEDP-4Na, 1 part of EDTA-FeNa, 3 parts of modified chitosan oligosaccharides, 1 part of sodium citrate, 1.3 parts of flavor, 1 part of 2.5% kason preservative, 0.5 parts of amino acid moisturizer, 0.2 parts of vitamin B6, and 0.01 parts of pigment.

5. A method for preparing the composite disinfectant preparation as claimed in claim 3 or 4, comprising the following steps: Liquid A: add 4 / 7 of the total weight of pure water into a container, heat to 65°C, stop heating, add EDTA-2Na, stir to fully dissolve; add AESA, stir to fully dissolve; add K12A, stir to fully dissolve; add APG1214, stir to fully dissolve; add LAO-30, stir to fully dissolve; add 7 parts of Tween 20, stir to fully dissolve; add LS-30, stir to fully dissolve; add glycerol, stir to fully dissolve; Liquid B: Add 2 / 7 of the total weight of pure water into a container, heat to 50°C, stop heating, add NaCl, stir to fully dissolve; add HEDP-4Na, stir to fully dissolve; add EDTA-2K, stir to fully dissolve; add EDTA-FeNa, stir to fully dissolve; add DTPA-5Na, stir to fully dissolve; Liquid C: Add the remaining water into the container, heat to 35°C, stop heating, add modified chitosan oligosaccharide, stir to fully dissolve; add flavor, stir to fully dissolve; add 2.5% kasone preservative, stir to fully dissolve; add amino acid moisturizer, vitamin B6, pigment, stir to fully dissolve; After the above three solutions are prepared and cooled to a temperature of 15-30℃, first slowly add liquid B into liquid A, stirring while adding, and mix thoroughly; then add liquid C, stirring while adding, and mix thoroughly. Let it stand for more than 24 hours to ensure that all bubbles are expelled, and finally form a viscous, colored solution with a pleasant smell.

6. Use of the modified chitosan oligosaccharide according to claim 1 in removing skin nuclides.

7. Use of the composite disinfectant preparation according to any one of claims 2 to 4 in removing radionuclides from the skin.

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